Onset of action of inhaled glucocorticoids on bronchial and alveolar nitric oxide output

Fractional exhaled nitric oxide (F_ENO) is a marker of airway inflammation. Measuring F_ENO at multiple flow rates enables calculation of NO parameters: bronchial NO output (J_awNO), bronchial wall (C_awNO) and alveolar (C_ANO) NO concentrations, and bronchial diffusion factor of NO (D_awNO). F_ENO is known to rapidly reduce after the commencement of inhaled corticosteroid (ICS) treatment. However, little is known on the effect of ICS on the other NO parameters. We assessed (1) the onset of action of ICS treatment on the NO parameters and (2) whether the changes in bronchial NO output are due to changes in bronchial wall NO concentration or diffusion factor. F_ENO and other NO parameters were measured at baseline and after 1, 3 and 7 d of treatment with inhaled fluticasone propionate 250 µg b.i.d. in 23 allergic children with a history of asthma-like symptoms. There was a decrease in J_awNO (from 680 (244/1791) (median (1st/3rd quartile)) to 357 (165/753) pl s⁻¹, p < 0.001) and F_ENO₅₀ (from 13.8 (7.5/35) to 8.3 (5.36/17.0) ppb, p < 0.001) in 3 d from the first dose of ICS. Also, C_awNO seemed to reduce after 3 d (from 171 (89/328) to 79 (54/157) ppb, p = 0.041), while D_awNO remained unchanged. Furthermore, C_ANO reduced during the 7 d treatment (from 3.0 (2.0/5.0) to 2.3 (1.9/2.6) ppb, p = 0.004). ICS treatment reduced F_ENO₅₀ and J_awNO rapidly and the decline was caused by decreased bronchial wall NO concentration while bronchial NO diffusion factor remained unchanged. These findings suggest that C_awNO could be a more specific marker of airway inflammation and treatment response than J_awNO or F_ENO₅₀, which are both determined also by D_awNO that seems to be resistant to the treatment with ICS.